Part II. Stochasticity and determinism in molecular and cell biology.
Key words: holistic, self-organization, molecular motors, networks, Brownian ratchet, protein translocation, gene expression, differentiation, nuclear organization, nonlinear thermodynamics , biased chaos, biosystem dynamics, emergence, steady-state organization, interpretation, paradigm shift, transcription, protein interactions, conjugate fluxes, moonlighting proteins, systems biology
A) Peer-reviewed publications on the topic:
1) Hypothesis/Review Kurakin, A. (2005) Self-organization vs Watchmaker: stochastic gene expression and cell diffrentiation. Dev. Genes Evol. 215(1): 46-52. (© Springer-Verlag) (156 KB)
(The original publication is available at springerlink.com)
2) Review Kurakin, A. (2005) Self-organization versus Watchmaker: stochastic dynamics of cellular organization. Biol. Chem. 386(3): 247-54. (92 KB)
3) Review Kurakin, A. (2005) Stochastic cell. IUBMB Life 57(2): 59-63. (176 KB)
4) Review Kurakin, A. (2006) Self-organization versus Watchmaker: molecular motors and protein translocation. Biosystems 84(1): 15-23. (296 KB)
5) Review Kurakin, A. (2007) Self-organization versus Watchmaker: ambiguity of molecular recognition and design charts of cellular circuitry. J. Mol. Recognition 20(4): 205-214. (3.9 MB)
Related material : "Preservation of adaptive plasticity across scales of biological organization: from molecules to societies" (webcast)
6) Research paper Kurakin A, Swistowski A, Wu SC, Bredesen DE (2007) The PDZ Domain as a Complex Adaptive System. PLoS ONE Sep 26; 2(9):e953. (Free access). doi: 10.1371/journal.pone.0000953
Related material : "The PDZ Domain as a Complex Adaptive System" (webacast)
Treacherous metaphors: Newton, Darwin and intelligent design. by Kurakin, A. (2005, Letter, unpublished)
C) Download the article ak030304 / Posted on March 3, 2004 :
Lecture7_Part II. Self-Organization versus Watchmaker: stochasticity and determinism in molecular and cell biology. (416 KB)
The paradigm can be defined as a self-consistent system of interrelated and interconnected concepts, principles, theories and postulates, which forms an interpretational framework for the description, modeling and comprehension of reality. Neither the minds of individual people, nor science or any branch of it can operate without a paradigm. The Cartesian-Newtonian paradigm underlying modern thought has dominated the minds of scientists and general public for more than three hundred years. This mechanistic, reductionist and deterministic paradigm states that a whole can and should be understood only through a study of its individual isolated parts. Philip Handler wrote in his book "Biology and the future of man": "One of the acid tests of understanding an object is the ability to put it together from its component parts. Ultimately, molecular biologists will attempt to subject their understanding of cell structure and function to this sort of test by trying to synthesize a cell" (Ref. 1).
We all have been brought up and educated in the tradition of Newtonian science. And we continue to live and to see the world through Newtonian glasses. It means that, consciously or subconsciously, we are trying to see mechanical devices and deterministic processes in everything around us. Our descriptions of the cell are full of mechanistic analogies. We see proteins produced like cars on assemblage lines according to programs encoded in the DNA, motors moving molecular complexes pre-assembled for specific tasks to defined destinations along microtubule tracks. Power stations producing and supplying energy where and when it is needed, recycling factories of proteosomal machines etc. It is very illustrative and helpful to look at the titles taken from our most respectful bioscience textbooks, scientific presentations and publications, to realize the all-pervasiveness of the mechanistic interpretation. What is the main idea underlying the most fashionable research today in molecular and cell biology? It is to make a comprehensive list of all components of the cell, see how they are connected and interlocked with each other and draw comprehensive engineering-looking charts as if the cell was clockwork and the molecules were gears and springs of a watch-like mechanism. The hope is that those charts will allow us to infer "the design" of the cell as soon as we have learned the functions and properties of its individual components. In other words, in biomedical sciences we sub-consciously perpetuate the image of the cell as clockwork and follow today a traditional reductionist approach dissembling the cell to individual basic units in order to understand the whole through the study of its isolated individual parts. Remarkably, while using mechanistic analogies and interpretations, we commonly ignore the idea that any mechanical device implies pre-existence of its design, and, therefore, a designer. The question "who is the designer?" is normally omitted from consideration by life scientists, probably in an attempt to mask from themselves the disturbing realization that science itself is not an isolated unity, but is always influenced by and is an inseparable part of the evolving social, political, cultural and economical context.
The inadequacy of the mechanistic interpretation of life is becoming increasingly obvious. Despite decades of intense biomedical research, over 25 billion dollars-yearly budgets of the National Institutes of Health only, and tera-bytes of fragmented experimental information we do not have any reasonably articulated mechanistic model of any human disease, be it a common cold or more complex ailments such as cancer, obesity or degenerative disorders. The modern high-throughput molecular technologies generate enormous and rapidly increasing amount of data opening novel research fields such as genomics, structural and functional proteomics, pharmaco-genomics, chemical genomics, metabolomics, etc. Unfortunately, most of the newly generated data cannot be integrated and comprehended with any reasonable degree of self-consistency within the interpretational framework of the current mechanistic paradigm.
The crisis of a dominating paradigm normally leads to the exploration and development of alternative interpretational systems. Just as the same pattern on the picture shown here can be perceived either as two faces or a vase, the same set of experimental data viewed from different paradigms gives rise to distinct perceptions of the same phenomena. I would like to discuss in this review examples of the same molecular phenomena that are considered from two different points of view: traditional mechanistic standpoint, and an alternative one that is based on a novel emerging view of biological systems treated as self-organizing fluxes or ever-evolving and dynamic organizations of interacting components.
It should be pointed out that the following chapters, which consider competing models and alternative perceptions of the same phenomena, are not intended to provide a comprehensive analysis of experimental data in order to decide in favor of one or another model or viewpoint. They are meant only to illustrate the idea that the mechanistic world perception and reductionism, which currently dominate our subconsciousness and dictate the choice of the questions we ask, the models we study and the interpretations we accept as scientifically sound, are becoming increasingly inadequate for description and comprehension of biological phenomena. It is the mechanistic paradigm and its underlying assumptions what causes confusion and inconsistencies in the studies discussed below and in many others left outside the scope of this review. The very progress in technology and methodology that allows us to probe the biological phenomena more accurately and to analyze them more precisely highlights and sharpens the inadequacy of mechanistic interpretations. The crisis of the old paradigm is concomitant with an emergence of the new interpretational framework that is being shaped today. Patterns of emerging paradigm are discussed throughout the review and summarized in the last chapter.